Asthma Treatment using Salbutamol and Mahuang

Asthma is a complex disorder involving biochemical, autonomic, immunologic, infectious, endocrine and psychological factors to varying degrees between individuals. It is an inflammatory disease characterised by airway hyper-responsiveness and episodic periods of bronchospasm.1 There are two types of asthma, extrinsic (immunologic) and intrinsic (autonomic).

Extrinsic asthma is caused by the release of inflammatory mediators from sensitised mast cells. Intrinsic asthma, however, is not characterised by such clearly defined precipitating factors. Attacks usually occur in people more than 35 years old and are triggered by factors such as infection, weather changes, exercise, inhaled allergens, emotion and allergic reactions to drugs such as aspirin.

When a doctor administers a synthetic drug, such as salbutamol, an exact dosage is based upon a patient’s body weight and age. Therefore, blood levels of the drug can be monitored easily for maximum therapeutic vs. toxic effect. It could be said that drug therapy is a cleaner form of herbal medicine. By isolating the active substances within known healing plants, the herb is replaced by a synthetic version, which contains some of the active plant’s ingredients.

The signs and symptoms of asthmatics are predominantly constant between each sufferer. Asthma is initiated by a type I, IgE immune response. The mast cells of the bronchial tissues release chemical mediators, histamine, slow-reacting substance of anaphylaxis, eosinophilic chemotactic factors, platelet-activating factors and prostaglandins. These produce bronchial smooth muscle spasm, vascular congestion, increased vascular permeability, oedema, production of thick tenacious mucus and an impaired mucociliary function. When combined with the epithelial cell damage caused by eosinophilic infiltration, it results in airway hyper-responsiveness. A combination of bronchospasm, mucosal swelling and excessive production of mucus obstructs the airways and increases the airflow resistance, especially on inhalation. As Mera stated, the symptoms of asthma include a persistent cough, recurrent episodes of dyspnoea, wheezing, tightness of the chest, a shortness of breath and a loss of energy due to excessive exertion on inhalation.2

The aim of this paper is to discuss the pathology of asthma from the viewpoints of Western and Chinese medicines. The pharmacological characteristics of salbutamol and Ma Huang (Ephedra Sinica) will be compared and discussed respectively.

Discussion

The most widely prescribed drug used in the treatment of acute asthma is salbutamol (albuterol). It is a sympathomimetic bronchodilator that relaxes the smooth muscle surrounding the bronchioles. There are various ways of administrating a dose of salbutamol, slow-releasing preparations, subcutaneous, intravenous or the preferred effective means of delivery, inhalation. A typical inhaled metered dose would include 100 μg/puff, usually one to two doses up to six times a day. Otherwise, 2.5-5 mg of salbutamol can be administered via a nebuliser in a sterile saline given over a 5-15 min period between 2 and 6 hours or as a dry powder. After inhalation, it will have an effect within 5-15 minutes. This effect may last up to 6 hours.

Salbutamol is a β-adrenoreceptor antagonist that binds to β-adrenoreceptors. By doing so, it prevents molecules from binding with the β-adrenoreceptors, hence the name β-blockers. Page et al state that salbutamol acts upon the β2 subtype of β-adrenoreceptors to cause bronchodilation.3 It is worth mentioning that salbutamol can work along side other drugs such as antimuscarinic agents and methylxanthines to achieve bronchodilation. Referring to figure 1 (a, b) we can see that the β2adrenoreceptor agonists relaxes the smooth muscle of the airways by activating the G protein-coupled receptors (c). This consequently leads to the activation of adenylyl cyclase and the generation of cyclic adenosine monophosphate (cAMP). Theophylline may relax the smooth muscle of the airways by inhibiting cAMP phosphodiesterase in the cell, thus increasing the intracellular concentrations of the protein kinase A (PK-A)..

When salbutamol is given to an asthmatic patient, the ratio of unchanged drug to metabolite in the urine after an oral dose is 1:2. Ritter et al go on to explain the pharmacokinetics of salbutamol.4 It undergoes pronounced presystemic metabolism in the intestinal mucosa and hepatic conjugation to from an inactive metabolite that is then excreted in the urine. Up to 80% of the aerosol-administered drug is actually swallowed, whist the remaining 10-20% remains as a free drug within the airways. The plasma elimination half-life is between 2 - 4 hours.

Henry shows how particular areas of the population need to vary their dosage: Infants and children should take a reduced dose along with patients over the age of 60.5 It can be passed by breast-feeding to an infant but does not pose any risk. Pregnant women have no adverse reaction. For the general population, its overdose danger rating and dependency is low. It has little stimulant effect upon the heart rate and blood pressure so making it safe for patients with heart problems or high blood pressure.

Adverse reactions to salbutamol include:

Fine skeletal muscle tremors,

Hypertension,

Vasodilation of blood vessels to skeletal muscle,

Palpitations,

Excitability,

Hypokalaemia, and

Tachycardia.

These adverse reactions are caused by salbutamol attaching to β-adrenoreceptors located in the heart, lungs and muscles. This is also the receptor site for epinephrine, thus any antagonist action by salbutamol will inhibit epinephrine action. This will lead to a decrease in cardiac output and metabolic rate.

Ma Huang

In the paradigm of Traditional Chinese Medical (TCM), Lung Qi deficiency and Wei Qi (defensive) deficiency can cause asthma. Unless these deficiencies are corrected, external pathogenic factors such as Wind, Heat, Cold, Damp, etc, can enter the body and disrupt Qi flow. Ma Huang facilitates Lung Qi flow and controls wheezing due to obstruction of Lung Qi by Wind and Cold. Ma Huang induces Lung Qi to flow more easily and causes it to descend, thereby stopping cough, reducing respiratory difficulty, and aiding the function of the Kidney in grasping Lung Qi.6 In TCM, failure of Kidney to grasp Lung Qi is another cause of asthma; if Lung Qi fails to descend, Kidney Qi cannot grasp it. Therefore, the effect of Ma Huang in facilitating Lung Qi to descent also benefits asthma caused by the failure of Kidney Qi to grasp Lung Qi. Ma Huang (figure 2) is the Chinese herbal equivalent to salbutamol. It can only be administered orally, within a mixed herbal formula, either in an herbal tea or tablet form. Ephedra sinica spp. are native to China, but other species grow in other Asian countries. The usual adult dose of Ma Huang is 3-10 g/day.

As Tang and Eisenbrand stated, the structural elements of Ma Huang vary depending upon its origin.7 Bensky et al list the main ingredients as ephedrine, pseudoephedrine, 1-N-methylephedrine, ephedrine, 1-norephedrine, d-N-pseudomethylephedrine, d-dimethylpseudoephedrine, benzyl-methylamine and 1-alpha-d-terpineol. Ephedrine is the main bronchodilatory agent in Ma Huang. From the native species of China, about 1% total alkaloid containing 63%-80% ephedrine and 20%-34% pseudoephedrine can be found.

Keys states that ephedrine dilates the bronchi, stimulates the respiratory centre and acts to prevent bronchial asthma.8 Its vasoconstrictive action shrinks congested mucous membranes. Structurally, ephedrine is very similar to epinephrine; it triggers the release of endogenous catecholamines from the post-ganglionic sympathetic fibres. It is absorbed well and is highly lipophilihc, it crosses the blood-brain barrier but its persistence is longer than that of epinephrine.9 Precautions should be taken for patients with prostatic hypertrophy, cardiac insufficiency and diabetes.

Tang et al reported an excretion rate of a typical oral dose of (-)-ephedrine of 88% in the first 24 hours and 97% within 48 hours; 53-74% of the drug was excreted unchanged, with N-demethylation to norephedrine occurring variably (8-20%).

As Bruneton mentions, excessive ephedrine use (as little as 15 ml of 1% solution) can induce spontaneous recovery from the common cold. However, possible side effects include dryness of the mouth, insomnia, sweating and anxiety. More seriously, it can cause psychic and cardiac alterations.